Exploring the Potential of IL-4 and IL-13 Plasma Levels as Biomarkers in Atopic Dermatitis.

Atopic dermatitis (AD) is a persistent inflammatory skin condition that impacts individuals of various age groups, including both children and adults. Its pathophysiology involves allergens penetrating a disrupted epidermal barrier, triggering the dermal cells to produce pro-inflammatory cytokines and eliciting a T-cell-mediated immune response. Notably, interleukins (ILs), particularly interleukin 4 (IL-4) and interleukin 13 (IL-13), play a key role in AD pathogenesis. Therapies directed at inflammatory mechanisms, including Dupilumab, have demonstrated notable effectiveness in enhancing skin lesions, alleviating subjective symptoms, and improving the overall quality of life for individuals with AD. Despite therapeutic advances, assessing AD severity remains challenging. The commonly used tools, such as the SCORAD and DLQI scores, rely on subjective patient responses. Paraclinically, the search for universal biomarkers continues, with efforts to identify reliable indicators reflecting disease severity and treatment response. Various biomarkers, including Th2-related chemokines and cytokines, have been explored, but none have gained universal recognition for routine clinical use. This study aims to investigate the dynamics of the plasma levels of IL-4 and IL-13 during Dupilumab treatment and establish correlations between these ILs and disease severity, as measured using the SCORAD and DLQI scores. The ultimate endpoint is to determine whether IL-4 and IL-13 can serve as reliable biomarkers, assessing their correlation with patient-reported feelings and disease activity and potentially influencing their inclusion or exclusion as diagnostic elements in routine clinical practice.

HPV and Other Risk Factors Involved in Pharyngeal Neoplasm-Clinical and Morphopathological Correlations in the Southwestern Region of Romania.

Oropharyngeal squamous cell carcinoma (OPSCC) development is strongly associated with risk factors like smoking, chronic alcohol consumption, and the living environment, but also chronic human papilloma virus (HPV) infection, which can trigger cascade cellular changes leading to a neoplastic transformation. The prevalence of these factors differs among different world regions, and the prevention, diagnosis, and prognosis of OPSCC are highly dependent on them. We performed a retrospective study on 406 patients diagnosed with OPSCC in our region that were classified according to the tumor type, localization and diagnosis stage, demographic characteristics, risk factors, and histological and immunohistochemical features. We found that most of the patients were men from urban areas with a smoking habit, while most of the women in our study were diagnosed with tonsillar OPSCC and had a history of chronic alcoholism. During the immunohistochemical study, we analyzed the tumor immunoreactivity against anti-p16 and anti-HPV antibodies as markers of HPV involvement in tumor progression, as well as the correlation with the percentage of intratumoral nuclei immunomarked with the anti-Ki 67 antibody in serial samples. We observed that the percentage of Ki67-positive nuclei increased proportionally with the presence of intratumoral HPV; thus, active HPV infection leads to an increase in the rate of tumor progression. Our results support the implementation of strategies for OPSCC prevention and early diagnosis and can be a starting point for future studies aiming at adapting surgical and oncological treatment according to the HPV stage for better therapeutic results.

Cutaneous Malignant Melanoma Metastatic to the Larynx and Trachea: A Case Report and Review of the Literature.

Malignant melanoma rarely develops in mucous membranes. Statistical data show that approximately 0.6-9.3% of patients with cutaneous malignant melanoma will develop metastases in the upper aerodigestive tract mucosa, and within these metastatic sites, the least common are the laryngeal and tracheobronchial ones. This exceedingly rare clinical entity has no clear treatment recommendations; radical surgery does not seem to benefit the patient in term of life expectancy. We present the case of a 56-year-old male patient diagnosed with laryngeal and tracheobronchial melanoma metastases. Prior to admission to our clinic the patient had a personal history of malignant melanoma of the nuchal region operated on 7 years ago, malignant melanoma of the gallbladder and metastatic left axillary polyadenopathy for which he underwent surgical treatment 3 months prior. Histopathological and immunohistochemical reports established the diagnosis of laryngeal metastasis of malignant melanoma. Genetic molecular analysis was positive for B-Raf (BRAF) gene and hence Vemurafenib was administered, with a favorable outcome at the one-year follow-up. Nevertheless, there are currently no clear universally accepted guidelines for the treatment of laryngeal melanoma, mainly due to the rarity of this clinical entity. We conducted a review of similar cases reported in the literature. Interestingly, reviewing the cases reported in the literature, it appears that laryngeal metastases of a primary cutaneous melanoma are more common in men, with an average time to metastasis of 4.3 years.

Kaposi's sarcoma of the larynx: case series.

Kaposi's sarcoma (KS) represents a type of cancer that usually arises on the skin and very rarely in other organs. KS-associated herpesvirus (KSHV), also known as human herpesvirus-8 (HHV-8) commonly arises in patients with acquired immunodeficiency syndrome (AIDS). Laryngeal involvement of KS is very rare. Our study comprised of three cases with laryngeal KS. All cases were solved through surgical excision of the tumor. Histopathological and immunohistochemistry examinations revealed laryngeal KS. Laryngeal KS should be managed through surgical resection, followed by oncological treatment.

Atopic Dermatitis with Multiple Comorbidities Treated with Dupilumab. A Case Report and Review of the Literature Regarding the Safety of Dupilumab.

Dupilumab is the only available biological treatment for moderate-to-severe atopic dermatitis (AD). Even so, limited clinical data regarding its safety profile are available. Interactions with other drugs and the adverse effects of Dupilumab on patients with multiple comorbidities, such as chronic heart disease, diabetes, chronic kidney disease, etc., are not known yet. Moreover, there have been described cases of cutaneous lymphomas induced by Dupilumab. Therefore, the clinician that wants to start treatment for moderate-to-severe atopic dermatitis, which does not respond to conventional drugs, might be reluctant to choose biologic agents such as Dupilumab. In this paper, we reported a case of severe atopic dermatitis with multiple comorbidities in which the patient was successfully treated with Dupilumab despite numerous underlying conditions. We also conducted a review of the current literature on the safety profile of Dupilumab in special categories of patients with comorbidities, such as heart, kidney, and liver disease, oncologic conditions, and during pregnancy.

Correlations between Morphology, the Functional Properties of Upper Airways, and the Severity of Sleep Apnea.

Obstructive sleep apnea (OSA) is considered the silent killer pathology of the new millennium. This is due to increased risk factors such as obesity. Healthcare systems face an increasing burden from severe cases of OSA. We performed a study on a group of 152 Romanian patients with OSA recording data obtained through polysomnography and cephalometric variables, recorded in lateral plain X-rays. The results confirmed some of the data available from previous studies worldwide, but some of the variables presented a positive statistical correlation specific to our study group. For example, the apnea-hypopnea index (AHI) correlated with the uvula length but surprisingly did not correlate with body mass index (BMI) because obesity tends to become endemic in Romania. To our knowledge, this is one of the first studies focusing on cephalometric data in Romanian OSA patients. The results obtained through this study will be further analyzed in research on larger groups of Romanian OSA patients.

Diagnosis and evolution of the benign tumor osteochondroma.

Osteochondroma represents a bone outgrowth covered by cartilaginous tissue and localized on the external surface of the bone. The incidence of osteochondroma is 20-35% of all pediatric benign tumors. Osteochondromas can be present in solitary or multiple forms and usually occur in the metaphysis of long bones in immature skeletons. The present study aimed to retrospectively determine the association between imaging diagnostic accuracy and histopathological examinations, which are the main methods of diagnosis for this type of tumor. A total of 66 patients presenting with radiological aspects of osteochondroma were initially selected; however, only the 56 patients who had a positive histopathological diagnosis of osteochondroma were eventually included in this study. Patient characteristics were taken into consideration and included age, sex, lesion localization, lesion imaging semiotics and histopathological aspects. Osteochondromas are generally asymptomatic lesions that are often incidentally diagnosed after trauma, which makes it difficult to determine the exact incidence of this pathology.

Erratum to "COVID-19 pandemic and alcohol consumption: Impacts and interconnections" [Toxicol. Rep. 8C (2021) 529 - 535/1078].

[This corrects the article DOI: 10.1016/j.toxrep.2021.03.005.].

COVID-19 pandemic and alcohol consumption: Impacts and interconnections.

Alcohol consumption is associated with multiple diseases and might contribute to vulnerability to SARS-CoV-2 infection. It can also catalyze exacerbations of mental and organic illnesses and predispose to behaviors with an increased risk of infection, severity of disease but also independently of sociopathic behavior and violence. Globally, millions of premature deaths from excessive alcohol consumption occur each year. This paper discusses the effects of increased alcohol consumption and the most important consequences on the health of the population during the social isolation and lockdown during current COVID-19 pandemic.

A Novel Nutraceutical Formulation Can Improve Motor Activity and Decrease the Stress Level in a Murine Model of Middle-Age Animals.

Ageing is a genetically programmed physiological process that is modulated by numerous environmental factors, associated with decreasing physiological function, decreasing reproductive rate and increasing age-related mortality rate. Maintaining mobility performance and physical function in the elderly is the main objective of the successful ageing concept. In this study, we aimed to evaluate the beneficial effect of a novel nutraceutical formulation containing Centella asiatica L. extract, vitamin C, zinc and vitamin D3 (as cholecalciferol) on motor activity and anxiety with the use of a murine model of old animals, as a means of providing proof for clinical use in the elderly, for enhancing physical strength and improving life quality. Eighteen Sprague Dawley 18 months old male rats were divided into three groups and received corn oil (the control group) or 1 capsule/kg bw Reverse supplement (treatment group 1) or 2 capsules/kg bw Reverse supplement (treatment group 2), for a period of 3 months. The Reverse supplement (Natural Doctor S.A, Athens, Greece) contains 9 mg Centella asiatica L. extract, vitamin C (200 mg as magnesium ascorbate), zinc (5 mg as zinc citrate), vitamin D3 (50 µg as cholecalciferol) per capsule. Before and after the treatment, the motor function and behavioral changes for anxiety and depression were evaluated using the open-field test, elevated plus-maze test and rotarod test. The supplementation with Reverse (Natural Doctor S.A) supplement can improve the locomotor activity in old rats in a dose-dependent manner, as demonstrated by an increase in the latency to leave from the middle square, in the number of rearings in the open field test, in the time spent in the open arms and time spent in the center in the elevated plus-maze test and the latency to all in all three consecutive trials in the rotarod test. Stress also decreased significantly in a dose-dependent manner, following the treatment with Reverse supplement, as was demonstrated by the decrease in the number of groomings at the open field test and time spent in the dark and the number of groomings at the elevated plus-maze test.

Prediction of Autoimmune Diseases by Targeted Metabolomic Assay of Urinary Organic Acids.

Autoimmune diseases (ADs) are chronic disorders characterized by the loss of self-tolerance, and although being heterogeneous, they share common pathogenic mechanisms. Self-antigens and inflammation markers are established diagnostic tools; however, the metabolic imbalances that underlie ADs are poorly described. The study aimed to employ metabolomics for the detection of disease-related changes in autoimmune diseases that could have predictive value. Quantitative analysis of 28 urine organic acids was performed using Gas Chromatography-Mass Spectrometry in a group of 392 participants. Autoimmune thyroiditis, inflammatory bowel disease, psoriasis and rheumatoid arthritis were the most prevalent autoimmune diseases of the study. Statistically significant differences were observed in the tricarboxylate cycle metabolites, succinate, methylcitrate and malate, the pyroglutamate and 2-hydroxybutyrate from the glutathione cycle and the metabolites methylmalonate, 4-hydroxyphenylpyruvate, 2-hydroxyglutarate and 2-hydroxyisobutyrate between the AD group and the control. Artificial neural networks and Binary logistic regression resulted in the highest predictive accuracy scores (66.7% and 74.9%, respectively), while Methylmalonate, 2-Hydroxyglutarate and 2-hydroxybutyrate were proposed as potential biomarkers for autoimmune diseases. Urine organic acid levels related to the mechanisms of energy production and detoxification were associated with the presence of autoimmune diseases and could be an adjunct tool for early diagnosis and prediction.

The Treatment of Cognitive, Behavioural and Motor Impairments from Brain Injury and Neurodegenerative Diseases through Cannabinoid System Modulation-Evidence from In Vivo Studies.

Neurological disorders such as neurodegenerative diseases or traumatic brain injury are associated with cognitive, motor and behavioural changes that influence the quality of life of the patients. Although different therapeutic strategies have been developed and tried until now to decrease the neurological decline, no treatment has been found to cure these pathologies. In the last decades, the implication of the endocannabinoid system in the neurological function has been extensively studied, and the cannabinoids have been tried as a new promising potential treatment. In this study, we aimed to overview the recent available literature regarding in vivo potential of natural and synthetic cannabinoids with underlying mechanisms of action for protecting against cognitive decline and motor impairments. The results of studies on animal models showed that cannabinoids in traumatic brain injury increase neurobehavioral function, working memory performance, and decrease the neurological deficit and ameliorate motor deficit through down-regulation of pro-inflammatory markers, oedema formation and blood-brain barrier permeability, preventing neuronal cell loss and up-regulating the levels of adherence junction proteins. In neurodegenerative diseases, the cannabinoids showed beneficial effects in decreasing the motor disability and disease progression by a complex mechanism targeting more signalling pathways further than classical receptors of the endocannabinoid system. In light of these results, the use of cannabinoids could be beneficial in traumatic brain injuries and multiple sclerosis treatment, especially in those patients who display resistance to conventional treatment.

Histopathological Features of Chronic Rhinosinusitis with Nasal Allergic Polyps.

Chronic rhinosinusitis with nasal polyps of allergic etiology is one of the most common pathology in the ENT sphere that affect a significant percentage of population. The paper aims to establish the involvement of the allergic component in the genesis of nasal polyposis. The study included 150 nasal polyps from patients hospitalized and operated in the ENT Department of Craiova's Clinical Emergency County Hospital. The biological material was fixed in 10% buffered formalin, processed by classical paraffin embedding technique followed by hematoxylin-eosin staining and it was interpreted in the Pathology Department of the same hospital. We evaluated a number of histopathological parameters that were given severity scores. The most common changes at epithelial level were: basal layer hyperplasia observed in 87 cases (58%), goblet cell hyperplasia in 121 cases (80.66%), basal membrane thickening with values between 10-42µm corresponding to a number of 118 cases (78.66%). The most important stromal changes were edema in 88% and infiltration with eosinophils 100%, indicating the allergic nature of this disease.

Rare amyloidoma of the tongue base: A case report and review of the literature.

Localized amyloidosis is a rare condition characterized by the deposition of misfolding protein in a tissue, without other systemic manifestations. Only a small number of cases of localized amyloidosis of the tongue have been reported to date, in contrast to systemic amyloidosis, in which localization on the tongue is common. This study presents a rare case of localized amyloidosis of the tongue (amyloidoma) and provides a summary of the known literature of localized amyloidosis. This study describes the case of a 36-year-old female who presented with a swelling of the tongue base. The diagnosis of amyloidoma was made based on the findings of the physical examination, head and neck MRI findings and the histopathological examination with Congo red stain under polarized light. The histopathological diagnosis was as follows: Localized lambda light-chain amyloidosis. A thorough physical examination was performed by the ENT and Hematology/Oncology departments, without revealing signs of systemic disease. A series of hematological and imaging tests were also performed to verify that there was no sign of systemic involvement. The patient declined surgical excision and the 2-year follow-up did not reveal any changes in tumor dimension. Although the etiology of localized amyloidosis is yet not clear, the prolonged reaction of tissue plasma cells to environmental antigens may be a causative factor for the initiation of the neoplastic process.

Imaging of the Posttraumatic Knee in Pediatric Patients.

Owing to its continuous transformation, the musculoskeletal system of pediatric patients presents some unique features with respect to both anatomy and physiology. The lesional pattern of the knee in pediatric patients is both similar to and in many aspects different from the lesional pattern in adults with knee injuries. In the case of pediatric patients, meniscal, tendinous and ligamentous lesions occur most frequently as a consequence of traumatic episodes. The purpose of the present study is to emphasize the importance of MRI examinations in pediatric patients exhibiting symptoms of knee joint injury. The imaging assessment of the extent of the lesions, which can be either simple or complex alterations, can directly influence the clinical management of these cases by appreciating the growth potential of the specific segment of immature skeleton involved.

Craniofacial morphology aspects in children with isolated growth hormone deficiency - a cephalometric study.

Craniofacial and dental morphology is influenced by different circulating hormones, but it is of particular importance that there is growth hormone (GH) in normal craniofacial and teeth development. Craniofacial morphometry studies in children with GH deficiency show different changes in certain anthropometric variables in the sense of reducing their values compared to normal children's developmental norms in different stages of childhood and adolescence. Therefore, the early establishment of GH replacement therapy can correct craniofacial morphological changes induced by GH deficiency. In our study, we evaluated different anthropometric craniofacial variables at children with GH deficiency and we established some anthropometric and morphological characteristics associated with this pathology.

Differences in the distribution of CD20, CD3, CD34 and CD45RO in nasal mucosa and polyps from patients with chronic rhinosinusitis.

The present study focused on the assessment of the inflammatory infiltrate that characterizes nasal polyps in patients with chronic rhinosinusitis and nasal polyposis. Inflammatory cell type was determined using specific markers. This evaluation was made possible by determining the expression of the following markers: CD20, a marker of B lymphocytes [using activated T cells (ATC) armed with CD20 antibody]; CD3, a marker of T lymphocytes (using ATC armed with anti­CD3 antibody); CD45, the leukocyte common antigen (using ATC armed with anti­CD45 antibody; and CD34, for the microvasculature of the nasal polyp (using anti­CD34 antibody). The diagnosis of chronic rhinosinusitis with nasal polyps (CRSwNP) was made according to current EPOS guidelines based on patient history, clinical examination and nasal endoscopy. We examined surgically resected nasal polyps from 127 patients diagnosed with CRSwNP, who benefited from surgical procedures at the Department of Otorhinolaryngology of our institution. The polyps were analyzed at the Department of Pathology of our institution utilizing histopathological and immunohistochemical methods as follows: Firstly, the tissues were paraffin­impregnated, sectioned and stained with hematoxylin and eosin. We then examined the expression of CD3, CD20, CD34 and CD45RO by immunohistochemistry with soluble labeled streptavidin biotin (LSAB)/horseradish peroxidase (HRP) complexes. We observed the following histopathological changes: The structure of the epithelium was evidenced by collagenous subjacent stroma with mixed areas, sometimes associated with hyaline zones. In all types of polyps, we also observed a diffuse underlayer or periglandular lymphoplasmacytic in filtrate composed predominantly from T lymphocytes and eosinophils. The histopathological changes suggest the chronic inflammation of the sinus mucosa, which was diffusely distributed in allergic polyps and with nodular distribution in fibro­inflammatory polyps. The number of B lymphocytes was greater in the fibro­inflammatory polyps. On the whole, the findings of this study indicate that the inflammatory infiltrate in nasal polyps from patients with CRSwNP is mainly composed of T cells and eosinophils in all types of polyposis. In addition, a diffuse distribution of allergic polyps and the nodular distribution of fibro­inflammatory polyps, and the hyperplasia of the seromucous glands was observed. The determination of CD20, CD3, CD34 and CD45RO could be used to assess the inflammatory infiltrate of the nasal poplyps in these patients.

The importance of BMP6 marker within the process of epithelial-mesenchymal transition in the pleomorphic adenoma of the salivary gland.

The pleomorphic adenoma is the most frequently encountered tumor of the salivary glands, representing between 45% and 75% of the total number of the tumors of the salivary glands. According to the literature, there are many studies on the immunohistochemical aspects of the myoepithelial cells, present in the pleomorphic adenoma of the salivary gland. A big diversity of mono and polyclonal antibodies, such as the cytokeratins, muscular proteins and other markers, has been used. In our study, we investigated the immunohistochemical aspect of bone morphogenetic protein 6 (BMP6) marker concerning 15 cases of pleomorphic adenomas of the salivary glands. In the immunohistochemical study, we used the paraffin blocks that served for obtaining the sections necessary for the classical histopathological processing by means of the usual stainings. The immunohistochemical study used the enzymatic detection and the LSAB 2 (Labeled Streptavidin-Biotin 2) System technique as the working method. In order to underline the process of epithelial-mesenchymal transition, we also used double sequential immunohistochemical reactions. By the use of the BMP6 marker, we intended to evaluate the reactivity of the various tumor components in the pleomorphic adenomas of the salivary gland, for this marker, taking into consideration its possible involvement in the process of the epithelial-mesenchymal transition. The maximum reactivity for BMP6 was recorded at the level of the normal, excretory, intratubular units, in the luminal cells of the proliferative ductal units, in the myxoid matrix, the cytoplasm of the myxoid stellate cells and the plasmacytoid matrix and the cytoplasm of the chondroid lacunar cells. Some of the cells belonging to the solid, proliferative areas, some of the abluminal cells, that are part of the proliferative ductal units and certain myxoid stellate or plasmocytoid cells contain the S100 protein, which would indicate the existence of some processes of mesenchymal epithelial÷myoepithelial transdifferentiation in the development of this type of salivary tumor. The BMP6 expression is specific to the serous acini salivary cells, which are the most specialized epithelial salivary gland cells. The study demonstrated that the mesenchymal epithelial÷myoepithelial potential of transdifferentiation of the luminal cells that make up the proliferative units is certified by the immunohistochemical expression of some BMP6 purely mesenchymal protein cells.

Clinical, Histological and Immunohistochemical Evaluation of Larynx Cancer.

Laryngeal cancer represents the malignant degeneration, of epithelial nature or from the connective tissue, which starts in the constitutive elements of the larynx. Cancer localization in the larynx represents between 1% and 3% of all malignant tumors and approximately 50% of ear, nose and throat (ENT) tumors. Squamous cell carcinoma is the most common form (around 95%) of laryngeal cancer, with high incidence in human males from southern and central Europe, Romania occupying one of the top places. MATERIAL AND METHODS: Our study consisted of 490 patients diagnosed with laryngeal cancer from 2010 to 2016. They have been clinically, histologically, immunohistochemically, genetically, therapeutically and prognostically analyzed. Suspended microlaringoscopy has been the standard, allowing tumor extension evaluation and biopsy. All specimens were microscopically analyzed in standard or special histology stainings. For unclear histology specimens, immunohistochemical stainings were performed. RESULTS AND DISCUSSIONS: Histological types have been represented as follows: 31 carcinomas in situ, 17 microinvasive carcinoma, 205 poorly differentiated carcinomas, 138 moderately differentiated carcinomas, 63 well differentiated carcinomas, 8 papillary carcinomas, 1 leiomyosarcoma, 1 chondrosarcoma, 6 basaloid squamous cell carcinomas, 4 verrucous carcinoma, 1 malignant melanoma. CONCLUSIONS: The study brings to light the importance of integrated clinical, morphological and genetic evaluation of laryngeal cancer, regarding tumoral invasion grading and establishing an adequate surgical and oncologic treatment. The importance of immunohistochemistry in laryngeal cancer concerns prognosis factors which correlate with the evolution and histopathological degree of the lesion. The analysis of tumor invasion can lead to the development of therapeutic conduct and the establishment of prognostic markers.

Expression pattern of CK7 and CK20 in nasal polyps, at patients with chronic rhinosinusitis with nasal polyposis.

We investigated the expression of cytokeratins 7 (CK7) and 20 (CK20) in nasal polyps on a group of 106 patients with chronic rhinosinusitis with nasal polyposis (45 women - 42% and 61 men - 58%) who benefited from surgical procedures. Harvested biological material was analyzed in the pathology laboratory through two methods: histopathological and immunohistochemical analysis. Classical histopathological method of processing the tissues initially fixed in 10% formalin was used. The tissues were then processed by paraffin impregnation, sectioned and stained with Hematoxylin-Eosin. The immunohistochemical method was based on soluble immunoenzymatic complexes - LSAB/HRP (labeled Streptavidin Biotin) method. We used DAKO LSAB 2 System HRP (Universal DAKO Labeled Streptavidin Biotin 2 System Horseradish Peroxidase). The expressions of CK7 and CK20 in nasal polyps were analyzed.